Practice Guidelines

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention has updated its strategy to eliminate hepatitis B virus (HBV) transmission in the United States. The report provides new recommendations to improve prevention of perinatal and early childhood HBV transmission, including implementation of universal infant vaccination beginning at birth, and to increase vaccine coverage among previously unvaccinated children and adolescents. The full report was published in the December 23, 2005, issue of Morbidity and Mortality Weekly Report and is available online athttp://www.cdc.gov/mmwr/preview/mmwrhtml/rr5416a1.htm.

A primary focus of the strategy is universal vaccination of infants to prevent early childhood infection and to eventually protect adolescents and adults from infection. Other components include routine screening of all pregnant women for hepatitis B surface antigen (HBsAg), postexposure immunoprophylaxis of infants born to HBsAg-positive women, vaccination of children and adolescents who were not previously vaccinated, and vaccination of unvaccinated adults at increased risk of infection.

According to recent estimates, more than 95 percent of pregnant women are tested for HBsAg, and case management has been effective in ensuring high levels of initiation and completion of postexposure immunoprophylaxis among identified infants born to HBsAg-positive women. Hepatitis B vaccine has been integrated successfully into the childhood vaccination schedule, and infant vaccine coverage levels are now equivalent to those of other vaccines in the childhood schedule.

Despite these successes, challenges remain. Even with improvements in the treatment of pregnant women, only about 50 percent of expected births to HBsAg-positive women are identified for case management. The need for proper treatment of women without prenatal care, including HBsAg testing at the time of admission for delivery and administration of the first dose of vaccine to infants within 12 hours of birth, is underscored by the higher prevalence of HBsAg seropositivity among these women than among women who are screened prenatally.

Recommendations

PREGNANT WOMEN

Pregnant women should be vaccinated against HBV if they are at risk of infection during pregnancy (i.e., if they had more than one sex partner during the previous six months, were evaluated or treated for a sexually transmitted disease, used injection drugs, or had an HBsAg-positive sex partner). Pregnant women at risk for HBV infection during pregnancy should be counseled about other methods to prevent HBV infection.

UNIVERSAL VACCINATION OF INFANTS

All infants should receive the hepatitis B vaccine series as part of the recommended childhood immunization schedule. All medically stable infants weighing at least 4 lb, 6 oz (2,000 g) at birth who are born to HBsAg-negative mothers should receive a first dose of vaccine before hospital discharge. Only single-antigen hepatitis B vaccine should be used for the birth dose.

On a case-by-case basis and only in rare circumstances, the first dose may be delayed until after hospital discharge in infants who weigh at least 2,000 g and whose mothers are HBsAg negative. When such a decision is made, a physician's order to withhold the birth dose and a copy of the original laboratory report indicating that the mother was HBsAg negative during the pregnancy should be included in the infant's medical record. Infants who do not receive a first dose before hospital discharge should receive the dose by no later than two months of age. The birth dose should not be delayed in infants whose mothers engaged in high-risk sexual or drug-using practices during pregnancy.

Preterm infants weighing less than 2,000 g at birth who are born to HBsAg-negative mothers should have their first vaccine dose delayed until one month after birth or hospital discharge. For these infants, a copy of the original laboratory report indicating that the mother was HBsAg negative during the pregnancy should be included in the infant's medical record.

The vaccine series should be completed with single-antigen vaccine or a combination vaccine that contains the hepatitis B vaccine antigen. The final dose in the vaccine series should not be administered before 24 weeks of age. Administration of four doses of hepatitis B vaccine is permissible in certain situations (e.g., when combination vaccines are administered after the birth dose). The first dose of hepatitis B vaccine should be administered at birth and the final dose at six to 12 months of age in populations with current or previously high rates of childhood HBV infection (i.e., Alaska Natives; Pacific islanders; and immigrant families from Asia, Africa, and other regions with intermediate or high endemic rates of infection).

CHILDREN AND ADOLESCENTS WHO WERE NOT PREVIOUSLY VACCINATED

Hepatitis B vaccination is recommended for all children and adolescents younger than 19 years. Children and adolescents who have not previously received hepatitis B vaccine should be vaccinated at any age with an appropriate dose and schedule. When selecting a vaccine schedule, physicians should consider the need to achieve completion of the vaccine series. In all settings, vaccination should be initiated even if completion of the vaccine series is not ensured.

Immunization records of all children 11 and 12 years of age should be reviewed, and the vaccine series should be completed if necessary. Immunization redcords should be reviewed for all children and adolescents younger than 19 years (including internationally adopted children) who were born in Asia, the Pacific islands, Africa, or other intermediate- or high-endemic countries or who have at least one parent who was born in one of these areas, and the vaccine series should be completed if necessary. In settings that provide health care services to adolescents, hepatitis B vaccine should be offered to all unvaccinated adolescents, particularly those who engage in behaviors that place them at high risk for HBV infection.

Vaccination Schedules

PREEXPOSURE VACCINATION

Infants and Children

Primary vaccination consists of at least three intramuscular doses of hepatitis B vaccine. Vaccine schedules for infants and children (Table 1) are determined on the basis of immunogenicity data and the need to integrate hepatitis B vaccine into a harmonized childhood vaccination schedule. The immunogenicity of the combined Haemophilus influenzae type B conjugate/hepatitis B vaccine (Comvax) and the combined diphtheria and tetanus toxoids and acellular pertussis/hepatitis B/inactivated poliovirus vaccine (Pediarix) is equivalent to that of their individual antigens administered separately. However, these vaccines cannot be administered to infants younger than six weeks; only single-antigen hepatitis B vaccine may be used for the birth dose.

note:This schedule applies to infants weighing at least 4 lb, 6 oz (2,000 g). A schedule for preterm infants weighing less than 2,000 g is provided in the full report of the Advisory Committee on Immunization Practices, which is available online at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5416a1.htm.

*—HepB vaccine, recombinant (Recombivax HB or Engerix-B) should be used for the birth dose. Comvax and Pediarix cannot be administered before six weeks of age.

†—HBIG (0.5 mL) is administered intramuscularly in a separate site from vaccine.

‡—The final dose in the series should not be administered before 24 weeks of age.

∮—Mothers should have blood drawn and tested for HBsAg as soon as possible after admission for delivery; if the mother is found to be HBsAg positive, the infant should receive HBIG as soon as possible but no later than seven days of age.

||—On a case-by-case basis and only in rare circumstances, the first dose may be delayed until after hospital discharge in an infant weighing at least 2,000 g whose mother is HBsAg negative, but only if a physician's order to withhold the birth dose and a copy of the mother's original HBsAg-negative laboratory report are documented in the infant's medical record.

Adapted from Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep 2005;54(RR16):9.

note:This schedule applies to infants weighing at least 4 lb, 6 oz (2,000 g). A schedule for preterm infants weighing less than 2,000 g is provided in the full report of the Advisory Committee on Immunization Practices, which is available online at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5416a1.htm.

*—HepB vaccine, recombinant (Recombivax HB or Engerix-B) should be used for the birth dose. Comvax and Pediarix cannot be administered before six weeks of age.

†—HBIG (0.5 mL) is administered intramuscularly in a separate site from vaccine.

‡—The final dose in the series should not be administered before 24 weeks of age.

∮—Mothers should have blood drawn and tested for HBsAg as soon as possible after admission for delivery; if the mother is found to be HBsAg positive, the infant should receive HBIG as soon as possible but no later than seven days of age.

||—On a case-by-case basis and only in rare circumstances, the first dose may be delayed until after hospital discharge in an infant weighing at least 2,000 g whose mother is HBsAg negative, but only if a physician's order to withhold the birth dose and a copy of the mother's original HBsAg-negative laboratory report are documented in the infant's medical record.

Adapted from Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep 2005;54(RR16):9.

The use of four-dose hepatitis B vaccine schedules, including schedules with a birth dose, has not increased vaccine reactogenicity. Anti-HBsAg responses after a three-dose series of hepatitis B–containing combination vaccines among infants who were previously vaccinated at birth with single-antigen hepatitis B vaccine are comparable to those observed after a three-dose series of combination vaccine without a birth dose.

Birth Dose

Hepatitis B vaccine can be administered soon after birth with no decrease in protective effectiveness and only minimal decrease in immunogenicity compared with administration at older ages. Administration of a birth dose of hepatitis B vaccine is required for effective postexposure immunoprophylaxis to prevent perinatal HBV infection. Although infants who require postexposure immunoprophylaxis should be identified by maternal HBsAg testing, administering a birth dose to infants even without hepatitis B immune globulin (HBIG) may prevent perinatal infection among infants born to HBsAg-positive mothers who are not identified because of testing or reporting errors. The birth dose also provides early protection to infants at risk of infection after the perinatal period. Administration of a birth dose has been associated with higher rates of on-time completion of the hepatitis B vaccine series.

Adolescents

Recommended vaccination schedules for adolescents balance available immunogenicity data with the need to achieve compliance with vaccination in this age group. Both of the licensed single-antigen hepatitis B vaccines administered intramuscularly at zero, one, and six months produce a seroprotection rate of more than 95 percent in adolescents. Equivalent seroprotection rates are achieved in adolescents vaccinated at zero, one to two, and four months or at zero, 12, and 24 months. The 10-mcg adult dose of hepatitis B vaccine, recombinant (Recombivax HB) administered in a two-dose schedule to adolescents 11 to 15 years of age at zero and ▴ four to six months produces antibody levels equivalent to those obtained with the 5-mcg dose administered on a three-dose schedule. However, no data on long-term antibody persistence or protection are available for two-dose schedules. No combination vaccines containing hepatitis B vaccine antigen are approved for use in adolescents 11 to 17 years of age.

Nonstandard Vaccine Schedules

No apparent effect on immunogenicity has been documented when minimum spacing of doses is not achieved precisely. Increasing the interval between the first two doses has little effect on immunogenicity or final antibody concentration. The third dose confers the maximum level of seroprotection but acts primarily as a booster and appears to provide optimal long-term protection. Longer intervals between the last two doses result in higher final antibody levels but might increase the risk for HBV infection among persons who have a delayed response to vaccination. No differences in immunogenicity have been observed when one or two doses of hepatitis B vaccine produced by one manufacturer are followed by doses from a different manufacturer.

Groups Requiring Different Vaccination Doses or Schedules

Preterm infants weighing less than 2,000 g at birth have a decreased response to hepatitis B vaccine administered before one month of age. Regardless of birth weight or gestational age, medically stable preterm infants at one month of age have a response to vaccination that is comparable to that of full-term infants.

Although data about the response of children on hemodialysis to vaccination with standard child doses are lacking, protective levels of antibody occur in 75 to 97 percent of those who receive higher dosages (20 mcg) on the three- or four-dose schedule. Humoral response to hepatitis B vaccination also is reduced in other children and adolescents who are immunocompromised (e.g., hematopoietic stem cell transplant recipients, patients undergoing chemotherapy, persons infected with human immunodeficiency virus). Modified dosing regimens, including a doubling of the standard antigen dose or administration of additional doses, might increase response rates. However, data on response to these alternative vaccination schedules are limited.

POSTEXPOSURE PROPHYLAXIS

Passive-active postexposure prophylaxis with HBIG and hepatitis B vaccine and active postexposure prophylaxis with hepatitis B vaccine alone are highly effective in preventing viral transmission after exposure to HBV. HBIG alone also has been proven effective in preventing HBV transmission, but with the wide availability of hepatitis B vaccine, HBIG typically is used as an adjunct to vaccination.

The major determinant of the effectiveness of post-exposure prophylaxis is early administration of the initial dose of vaccine; the effectiveness diminishes the longer it is initiated after exposure. Studies are limited on the maximum interval after exposure during which postexposure prophylaxis is effective, but the interval is unlikely to exceed seven days for perinatal and needle-stick exposures and 14 days for sexual exposures.

LONG-TERM PROTECTION AND BOOSTER DOSES

Studies are needed to assess long-term protection after vaccination and the possible need for booster doses of vaccine. The longest follow-up studies of vaccine protection have been conducted in populations with an initially high endemicity of HBV infection. Implementation of hepatitis B vaccination programs in populations with a high endemicity of HBV infection has resulted in virtual elimination of new HBV infections by providing vaccine-induced immunity to susceptible persons. In these populations, ongoing exposure of vaccinated persons to persons with chronic HBV infection might complicate future efforts to assess long-term hepatitis B vaccine effectiveness. Assessment of effectiveness provided by hepatitis B immunization after 15 to 20 years will require studies among populations that continue to have exposures to HBsAg-positive persons (e.g., communities of immigrants from highly endemic countries, populations of injection-drug users, health care professionals) and studies among populations with a low prevalence of infection.

Prevention and Management of Perinatal HBV Infection

All pregnant women should be tested for HBsAg during an early prenatal visit (e.g., first trimester) in each pregnancy, even if they have been vaccinated or tested previously. Women who were not screened prenatally, those who engage in behaviors that put them at high risk of infection, and those with clinical hepatitis should be tested at the time of admission to the hospital for delivery.

Women who are HBsAg positive should be referred to an appropriate case-management program to ensure that their infants receive timely postexposure prophylaxis and follow-up. In addition, a copy of the original laboratory report indicating the pregnant woman's HBsAg status should be provided to the hospital where delivery is planned and to the health care professional who will care for the newborn.

When HBsAg testing of pregnant women is not feasible (e.g., in remote areas without access to a laboratory), all infants should receive hepatitis B vaccine within 12 hours of birth and should complete the hepatitis B vaccine series according to a recommended schedule for infants born to HBsAg-positive mothers.

INFANTS BORN TO HBSAG-POSITIVE MOTHERS

All infants born to HBsAg-positive women should receive single-antigen hepatitis B vaccine and HBIG (0.5 mL) within 12 hours of birth, administered at different injection sites. The vaccine series should be completed according to a recommended schedule for infants born to HBsAg-positive mothers. The final dose in the vaccine series should not be administered before 24 weeks of age.

For preterm infants weighing less than 2,000 g, the birth dose should not be counted as part of the vaccine series because of the potentially reduced immunogenicity of hepatitis B vaccine in these infants; three additional doses of vaccine (for a total of four doses) should be administered beginning when the infant is one month of age.

Postvaccination testing for antibodies to HBsAg (anti-HBsAg) and HBsAg should be performed after completion of the vaccine series, at nine to 18 months of age (generally at the next well-child visit). Testing should not be performed before nine months of age to avoid detection of anti-HBsAg from HBIG administered during infancy and to maximize the likelihood of detecting late HBV infection. Testing infants for antibodies to hepatitis B core antigen (anti-HBc) is not recommended because passively acquired maternal anti-HBc might be detected in infants born to mothers infected with HBV.

Infants of HBsAg-positive mothers may be breastfed beginning immediately after birth.

INFANTS BORN TO WOMEN WITH UNKNOWN HBSAG STATUS

Women admitted for delivery without documentation of HBsAg test results should have blood drawn and tested as soon as possible after admission. While test results are pending, all infants born to women without documentation of HBsAg test results should receive the first dose of single-antigen hepatitis B vaccine (without HBIG) within 12 hours of birth. If the mother is found to be HBsAg positive, her infant should receive HBIG as soon as possible but no later than seven days of age, and the vaccine series should be completed according to a recommended schedule for infants born to HBsAg-positive mothers. If the mother is found to be HBsAg negative, the vaccine series should be completed according to a recommended schedule for infants born to HBsAg-negative mothers. If the mother has never been tested to determine her HBsAg status, the vaccine series should be completed according to a recommended schedule for infants born to HBsAg-positive mothers. Administration of HBIG is not necessary for these infants.

Because of the potentially decreased immunogenicity of vaccine in preterm infants weighing less than 2,000 g, these infants should receive single-antigen hepatitis B vaccine and HBIG (0.5 mL) if the mother's HBsAg status cannot be determined within 12 hours of birth. The birth dose of vaccine should not be counted as part of the three doses required to complete the vaccine series; three additional doses of vaccine (for a total of four doses) should be administered according to a recommended schedule on the basis of the mother's HBsAg test result.